The kinetics and biochemistry of the recovery from radiation- induced cycle delay are to be studied as a function of stage in the cell cycle in synchronized Chinese hamster cells utilizing the mitotic cell collection procedure to precisely analyze the kinetics of division delay, and the incorporation of 3HTdR and subsequent liquid scintillation counting and autoradiography (CPM/labeled cell) to analyze the perturbation of DNA replication (S delay). The following questions are being asked: 1. What is the nature of the two components repair process of radiation-induced division delay? At what level of damage does the rapid, initial repair process become operant? Does the recovery from radiation-induced S delay exhibit the same kinetics as the recovery from division delay? The activation energy of the repair process for division delay in asynchronous populations is 11,000 cal/mole, is it the same for radiation-induced S delay? Does the activation energy of the repair process vary with cell age? These answers will be derived from synchronized Chinese hamster cells by varying the size of the first dose in two dose fractionation schemes combined with sub-optimal temperatures during the fractionation interval. 2. What is the effect of inhibiting RNA or protein synthesis on the cycle delay repair processes? Answers will be attained by the respective application of lucanthone or cycloheximide between two radiation dose-fractions. 3. What are the kinetics and the biochemical nature of the recovery from hyperthermia-induced cycle delay? How does the damage from radiation and the damage from hyperthermia interact at the level of impaired cycle progression? Answers will be made available by fractionating heat treatments and by fractionating heat and radiation. 4. What is the effect of gene dosage on the recover from radiation induced and heat-induced cycle delay? This experimental system will provide an answer through the applicaton of two dose fractionation to our strain of tetraploid Chinese hamster cells. With this information in hand we will understand more clearly the role of cell cycle progression, parasychronization, and repopulation betveen fractionated doses of irradiation, and hence be able to predict how these parameters might be more fully utilized to enhance the effectiveness of radiation in human cancer therapy.